Genmab reports 75% first-line response in petosemtamab colorectal study
The single-arm analysis includes unconfirmed responses and supports two enrolling Phase 3 trials; median response duration was not disclosed.
Adrian Kessler
Tumour responses reached 75 per cent in previously untreated metastatic colorectal cancer as Genmab A/S NASDAQGMAB reported updated Phase 2 petosemtamab findings on Sunday. The second-line response rate was 67 per cent, but both figures include unconfirmed responses.
The Oct. 25 release describes petosemtamab combined with chemotherapy in an uncontrolled study. Genmab said most previously unconfirmed responses were subsequently confirmed, without providing an updated confirmed-only rate, and scheduled an investor update for Oct. 28.
Genmab is a Copenhagen-based international biotechnology company developing antibody medicines for cancer and other serious diseases.
Its U.S. depositary shares closed at US$43.79 on Nasdaq at 4:00 p.m. EDT on Oct. 23, according to Google Finance NASDAQGMAB. That close preceded Sunday's findings and cannot establish a market reaction.
Follow-Up Does Not Establish Response Duration
The analysis used a May 15 data cutoff and covered 79 treated patients. Of those, 45 received first-line treatment and 34 received second-line treatment; the release does not specify the efficacy-evaluable denominators behind the response rates.
Patients had RAS/BRAF wild-type disease and had not previously received an EGFR-targeting treatment. They received petosemtamab, an experimental antibody targeting EGFR and LGR5, with FOLFOX or FOLFIRI chemotherapy; investigator-assessed response and safety were primary endpoints.
Median follow-up was 5.9 months in first-line treatment and 7.1 months in second-line treatment. At the cutoff, 76 per cent and 74 per cent, respectively, remained on treatment.
Those follow-up periods measure observation time, rather than how long responses lasted. The release supplies no median response duration, progression-free survival result, confidence interval or p value, and has no control arm. These findings therefore do not establish petosemtamab's added benefit over chemotherapy.
"The confirmation of previously unconfirmed responses with longer follow-up further reinforces the durability of responses observed across treatment lines and strengthens our confidence in petosemtamab," Genmab chief medical officer Tahamtan Ahmadi said in the release.
Drug-related adverse events led to petosemtamab discontinuation in 5 per cent of the modified FOLFOX6 group and 3 per cent of the FOLFIRI group. Grade 3 infusion reactions occurred in 7 per cent and 3 per cent, respectively; no treatment-emergent adverse events leading to death were reported.
The distinction between response rates and response duration also features in the ESMO lung-cancer readouts.
Read more: Lilly reports 14.5-month response duration with olomorasib lung-cancer combination
Colorectal Trials Address Different Mutation Groups
Genmab says its Phase 3 LiGeR-CRC1 and LiGeR-CRC2 studies are enrolling first- and second-line colorectal cancer patients, respectively. Sunday's release reports no FDA feedback endorsing the study design or establishing a colorectal approval pathway.
The findings concern a different population from the Oct. 24 collaboration with Incyte Corporation NASDAQINCY. That agreement covers a planned Phase 1/2 combination of petosemtamab, Incyte's KRAS G12D inhibitor INCB161734 and chemotherapy in mutation-positive colorectal cancer, rather than the wild-type population reported on Sunday.
Read more: Genmab and Incyte agree to colorectal cancer combination trial
Genmab's Aug. 6 interim report recorded US$1.503 billion in cash and cash equivalents at June 30. Sunday's clinical release gives no cash-runway estimate or budget for completing the colorectal trials.
For sector context, the iShares Biotechnology ETF NASDAQIBB closed at US$207.74 at 4:00 p.m. EDT on Oct. 23, according to Google Finance. That benchmark also predates the findings.
The next scheduled checkpoint is Genmab's Oct. 28 investor update, an opportunity for management to clarify response confirmation and the Phase 3 timetable. Sunday's release sets no date for comparative colorectal results.
